Male mice on a lifelong folate-deficient diet display epigenetic alterations - modifications of DNA by chemical groups - to their sperm DNA reports a study in Nature Communications this week. In some cases, these mice sire offspring with developmental abnormalities, such as craniofacial defects and spinal deformities. This work provides new understanding as to the possible paternal routes to developmental defects.

Epigenetic DNA alterations, such as DNA methylation, change gene activity without affecting the sequence of the DNA. Previous work has shown that dietary folate can influence levels of cellular DNA methylation and gene expression and, in addition, paternal diet can alter the metabolism of the offspring. Sarah Kimmins and her team fed male mice a folate-deficient diet throughout their entire life and show that this leads to alterations in the methylation of the males’ sperm DNA and to reduced fertility. Further, both male and female offspring of these males had a higher frequency of developmental abnormalities than offspring of males on a normal diet. They note, however, that the mechanism of epigenetic transmission and therefore the molecular causes of the developmental defects are unclear.